Rare Events

Detection of Rare Cells

The two main situations which take particular advantage of automatic slide scanning are rare event detection and statistical scoring of a large number of cells. The detection of fetal nucleated red blood cells (fNRBCs) in maternal blood presents an example of an extremely rare event; another example would be the evaluation of circulating tumor cells (CTCs) for tumor staging and therapy monitoring. Speed is essential in rare cell detection. The amazing scanning speed of Metafer eliminates the need for enrichment, which is very desirable as there is an inherent risk of losing cells of interest.

Fetal Cells

Isolating fetal nucleated red blood cells (fNRBCs) from the maternal blood facilitates prenatal genetic analysis without the need for procedures that are invasive for the fetus. Such isolation usually involves specific antibody labeling and a technique for finding the extremely rare target cells in the sample. It could be shown that automated microscopy, the core skill of MetaSystems, is a feasible method for detecting fNRBCs. MetaSystems has developed algorithms to quickly and precisely detect rare events.

For the detection of rare fetal cells, Metafer scans several thousands of cells per second. All detected objects are stored with their positions on the slide along with a gallery image. The system detects rare fetal cells based on their staining pattern. Scanning is performed in the primary signal channel. Specific staining patterns such as ring-shaped, membrane bound antibody staining are precisely identified. A second signal color channel can be used for confirming the detected object. Additionally, counter stain signals are used to distinguish the finding from extracellular debris.

Circulating Tumor Cells

Circulating tumor cells (CTCs) are cells that have migrated away from a primary tumor into blood or the lymphatic system, and are transported and circulated around the body. CTCs are believed to be the origin of additional tumors (metastases) in distant organs causing the vast majority of cancer-related deaths. It is consensus that detection of CTCs may have important prognostic and therapeutic implications.

Metafer's ability to detect rare events in the fastest time makes it a perfect tool for finding CTCs. But the system can do much more than localizing the cells. Each detected object in Metafer is related to its position on the sample. Thus, a gallery of detected CTCs, for example, is also a position list for subsequent scans. It is therefore possible to let Metafer relocate the tumor cells and to perform further automated tasks, such as FISH signal analysis or even to lift cells off the slide by microdissection. With this ability, the identified cells can be investigated thoroughly to gain additional information on their origin.

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